The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta

M L Webb; K E Dickinson; C L Delaney; E C Liu; R Serafino; R B Cohen; H Monshizadegan; S Moreland

doi:10.1016/0006-291x(92)91710-8

The endothelin receptor antagonist, BQ-123, inhibits angiotensin II-induced contractions in rabbit aorta

Biochem Biophys Res Commun. 1992 Jun 30;185(3):887-92. doi: 10.1016/0006-291x(92)91710-8.

Authors

M L Webb¹, K E Dickinson, C L Delaney, E C Liu, R Serafino, R B Cohen, H Monshizadegan, S Moreland

Affiliation

¹ Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J. 08543-4000.

PMID: 1320879
DOI: 10.1016/0006-291x(92)91710-8

Abstract

The purpose of this study was to examine the specificity of the cyclic pentapeptide ET(A) receptor antagonist BQ-123. BQ-123 competitively antagonized endothelin-1-induced contractions in rabbit aorta, increases in inositol phosphates in cultured rat vascular smooth muscle A10 cells, and binding of [125I]endothelin-1 to the cloned ETA receptor cDNA expressed in Cos 7 cells. In contrast, BQ-123 was a weak antagonist of [125I]endothelin-3 binding to rat cerebellar membranes and to membranes from Cos 7 cells transfected with the cloned ETB receptor cDNA. BQ-123 shifted concentration-response curves in isolated rabbit aorta elicited by angiotensin II, but did not bind to angiotensin II receptors nor affect angiotensin II-induced increases in inositol phosphates. BQ-123 also did not affect contractions induced by KCl or norepinephrine. These data suggest that endothelin may play a role in angiotensin II-induced contractions of rabbit aorta.

MeSH terms

Angiotensin II / antagonists & inhibitors
Angiotensin II / pharmacology*
Animals
Aorta, Thoracic / drug effects
Aorta, Thoracic / physiology*
Cell Line
Cell Membrane / metabolism
Cells, Cultured
Cerebellum / metabolism*
Cloning, Molecular
Endothelins / pharmacology*
Endothelins / physiology
In Vitro Techniques
Inositol Phosphates / metabolism*
Kinetics
Muscle Contraction / drug effects*
Muscle, Smooth, Vascular / drug effects
Muscle, Smooth, Vascular / physiology*
Norepinephrine / pharmacology
Peptides, Cyclic / pharmacology*
Potassium Chloride / pharmacology
Rabbits
Receptors, Cell Surface / antagonists & inhibitors
Receptors, Cell Surface / metabolism
Receptors, Cell Surface / physiology*
Receptors, Endothelin
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / metabolism
Transfection

Substances

Endothelins
Inositol Phosphates
Peptides, Cyclic
Receptors, Cell Surface
Receptors, Endothelin
Recombinant Proteins
Angiotensin II
Potassium Chloride
cyclo(Trp-Asp-Pro-Val-Leu)
Norepinephrine